Drug-Eluting Balloon Treatment vs. Guideline-Directed Medical Therapy for the Treatment of Lipid-Rich Plaques

Drug-Eluting Balloon Treatment Versus Guideline-Directed Medical Therapy for the Treatment of Lipid-Rich Plaques: A Randomized Controlled Trial

The goal of this clinical trial is to find out whether treating vulnerable plaques in the coronary arteries with a drug-coated balloon can make them less dangerous than using standard medication alone. The study includes adults with acute coronary syndrome (a type of heart problem caused by reduced blood flow in the coronary arteries).

The main questions the study aims to answer are:

• Does the drug-coated balloon reduce the amount of fat inside the plaque more than medication alone?
• Is this treatment safe for patients?

Participants will:

• Undergo imaging of their coronary arteries during their planned heart procedure (PCI)
• Be randomly assigned to receive either a drug-coated balloon treatment or no extra treatment
• Undergo a heart scan (CT scan of the coronary arteries) within 2 weeks and again around 9 months after the procedure.
• Undergo a second heart catherization 9 months later to examine changes in the plaque.

Rationale:

Acute coronary syndromes (ACS) are often caused by rupture or erosion of certain high-risk vulnerable plaques. These plaques demonstrate specific features, such as a large lipid-rich necrotic core, a thin fibrous cap, and inflammation. Half of patients presenting with non-ST-segment elevation ACS have an additional vulnerable plaque, which increases their risk for non-culprit events during follow-up. Coronary intravascular ultrasound (IVUS) with the addition of near-infrared spectroscopy (NIRS) enables the identification of coronary lesions with high lipid content, quantified using the lipid-core burden index (LCBI) and is therefore able to distinguish plaques at risk to cause future non-culprit events. In addition, computed tomography coronary angiography (CCTA) is a non-invasive imaging modality that can identify high-risk plaque characteristics such as positive remodeling, low attentuation plaque, napkin-ring sign, and spotty calcification. Incorporating CCTA into this trial offers a unique opportunity to explore the potential of AI-based quantitative CT (AI-QCT) paramters by comparing them to IVUS-NIRS findings and clinical outcomes, which may support the future role of CCTA as a non-invasive tool for identifying and monitoring vulnerable plaques.

The main question remains whether local and systemic treatment of such high-risk plaques decreases the risk for adverse clinical outcome.

In our previous pilot study, DEBuT-LRP, we demonstrated that it was safe and feasible to treat vulnerable lipid-rich plaques with a drug-coated balloon (DCB) and that it was able to reduce the maximum LCBI on a 4 mm segment (maxLCBI4mm) after 9 months. In this randomized controlled trial, we intend to investigate the impact of DCB treatment on the maxLCBI4mm of lipid-rich plaques when compared to guideline-directed medical therapy alone.

Objective:

To test the hypothesis that paclitaxel-coated balloon treatment of non-obstructive non-culprit vulnerable lipid-rich plaques (LRP) leads to a greater reduction of the lipid-core burden index than guideline-directed medical therapy alone.

Study design:

A prospective two-arm randomized controlled trial.

Study population:

Patients older than 18 years with ACS who are scheduled for invasive percutaneous coronary intervention (PCI) of a native coronary artery.

Intervention:

DCB treatment of LRP in addition to guideline-directed medical therapy (GDMT).

Main study parameters:

The main study endpoint is the difference in maxLCBI4mm reduction from baseline to 9 months follow-up compared between the two randomization groups.

Secondary study endpoints are clinical safety endpoints (1. Flow-limiting dissection related to DCB-treatment necessitating bail-out stenting; 2. Periprocedural myocardial infarction; 3. Bleeding; 4. LRP lesion failure: cardiovascular death, myocardial infarction or repeat revascularization related to the index LRP, 5. Patient-oriented outcome: all-cause death, myocardial infarction or repeat revascularization) and imaging endpoints (1. IVUS-derived parameters; 2. QCA endpoints; 3. NIRS analyses of non-treated vessels; 4. CCTA-derived parameters).

Inclusion Criteria:

• Presenting with acute coronary syndrome (ACS);
• Successful PCI of a native coronary artery or major side branch;
• At least 2 native coronary arteries are accessible for invasive coronary imaging; i.e. not totally occluded and >2 mm and <6 mm reference vessel diameter.

Exclusion Criteria:

• Hemodynamically unstable (presence of cardiogenic shock, need for intubation, need for inotropes);
• Known hypersensitivity to paclitaxel;
• Procedural complications of the index PCI;
• Known renal insufficiency, i.e. eGFR <30 mL/min/1.73 m2;
• Hypersensitivity or allergy to contrast with inability to administer steroid and antihistamine premedication;
• Presence of a comorbid condition with a life expectancy of less than one year;
• Body weight >250 kg;
• Subject belonging to a vulnerable population (per investigator's judgment, e.g., subordinate hospital staff) or is unable to read or write.